Total neoadjuvant therapy for locally advanced rectal cancer: A western Australian experience.
Authors: Oliver Oey, Adnan Khattak, Tom Ferguson, Mary Theophilus, Siaw Sze Tiong, Sayed Ali, Yasir Khan
Journal: Journal of Clinical Oncology (2023)

e15582 Background: Despite the widespread application of standard chemoradiotherapy (CRT) followed by total mesorectal excision with adjuvant chemotherapy, the mortality reduction for locally advanced rectal cancer (LARC) has slowed in recent years. Total neoadjuvant therapy (TNT) is a novel therapeutic strategy in LARC which incorporates both systemic chemotherapy and neoadjuvant CRT prior to surgery. Recent studies have associated TNT with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates. However, real-world experience with TNT in the management of LARC remains limited. Methods: Records from patents with LARC who underwent TNT at two oncology centres in Western Australia since 2018 were screened. Patient demographics, diagnostic workup, treatment regimens, surgical, pathological reports, post-operative surveillance scans and adverse effects’ documentation were reviewed. TNT regimens included neoadjuvant chemotherapy (NAC) with oxaliplatin in combination with either 5-FU (FOLFOX) or capecitabine (CAPOX) with chemoradiation given prior or after NAC, which is then followed by surgery. Patients who had radiological complete response (rCR) were given the option of “watch and wait (W&amp;W)” instead of proceeding to surgery. Outcomes assessed included radiological complete response (rCR), pathological complete response (pCR) rate, proportion of patients with progressive disease, type of surgery, rate of R0 resection, proportion of patients who completed planned cycles of chemotherapy and radiotherapy and treatment-related adverse effects. Results: 29 patients with LARC have thus far have completed TNT followed by surgery. The mean age was 59 years (range 34-84), 58% and 42% of patients were male and female respectively. 11 (38%), 16 (55%) and 2 (7%) patients were ECOG 0, 1 and 2 respectively. The majority of patients were stage 3 (90%), with the remaining 3 patients at stage 1, 2 and 4 at time of presentation. 3 (10%) and 7 (24%) patients had pCR and rCR respectively, of which 4 opted for W&amp;W approach. Treatment was well-tolerated with 86% and 96% of patients completing the planned total course of chemotherapy and radiotherapy respectively although dose reductions and/or delay were required for many. Common adverse effects included neuropathy, neutropenia, anaemia and fatigue, most of which were grade 1. Of the 22 patients who underwent surgery, 19 (82%) and 4 (18%) patients had R0 resection and R1 resection respectively. Majority of the patients who underwent surgery had an anterior resection with temporary loop ileostomy (64%) while the remaining had an abdominoperineal resection (36%). After a median follow up time of 27 months, 10 (34%) patients had progressive disease. Conclusions: TNT is a well-tolerated, effective and promising strategy for the management of LARC. Further data is needed to determine the standard TNT protocol.